“Arteriosclerosis” refers to the thickening and hardening of arteries. “Atherosclerosis” is a type of arteriosclerosis in which cells including smooth muscle cells and macrophages, fatty substances, cholesterol, cellular waste product, calcium and fibrin build up in the inner lining of a body vessel. If unstable or prone to rupture, the resultant build-up is commonly referred to as vulnerable plaque. It is generally believed that atherosclerosis begins with damage to the inner arterial wall resulting in a lesion. At the damaged site, substances such as lipids, platelets, cholesterol, cellular waste products and calcium deposit in the vascular tissue may accumulate, leading to plaque progression and potentially the formation of vulnerable plaque. In turn, these substances lead to recruitment of cells involved in the inflammatory cascade of the immune system, such as macrophages, which may release substances leading to plaque destabilization.
Artherosclerotic lesions are characterized by a high content of macrophages which contribute to atherosclerosis by, for example, releasing free radicals, synthesizing bioreactive lipids, synthesizing complement components, synthesizing coagulation cascade components, secreting proteases and protease inhibitors, secreting cytokines and chemokines and phagocytosis of apoptic cells.
“Apoptosis” is the disintegration of cells into membrane-bound particles that are then eliminated by phagocytosis or by shedding. Research studies suggest that nitric oxide induces macrophage cell apoptosis. For example, a recent study has shown that the oral administration of L-arginine, a substrate which releases nitric oxide, results in increased apoptosis of macrophage cells (Wang et al., 1999. Circulation 99; 1236-1241). Thus, macrophage apoptosis at lesioned sites of a body vessel is therefore desirable.